Abstract

Abstract Selectin mediated tethering is one of the earliest steps in T cell entry to lymph nodes (LNs). Selectin binding is dependent on the synthesis of the sialyl Lewis X (sLex) structure, which requires the activity of several glycosyltransferases, including fucosyltransferases -IV and -VII. Mice deficient in expression of both enzymes (FtDKO) reveal profound impairment in T cell trafficking to LNs. We show that T cells isolated from FtDKO LNs were predominantly “memory/effector” (CD44Hi) cells. We analyzed the generation of effector and memory CD8 T cells in FtDKO mice following infection with LCMV. At day 8, the proportion of Ag-specific cells was similar in LNs of FtDKO mice compared to WT. In contrast, at day 60 p.i., we observed ~5-fold increase in the proportion of Ag-specific memory CD8 T cells in LNs of FtDKO. We then examined whether Ag-specific memory CD8 T cells were able to selectively enter LNs of FtDKO recipient mice. Memory CD8 T cells were profoundly impaired in entry to the LNs of FtDKO mice. Additionally, while we measured no differences in exit rate of naïve and memory CD8 T cells out of the LNs, we found more naïve T cells entered the LNs from the blood compared to memory. We hypothesize that an unknown mechanism leads to the selective retention of memory T cells in FtDKO LNs.

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